Experimental Treatment of SIV-Infected Macaques via Autograft of CCR5-Disrupted Hematopoietic Stem and Progenitor Cells

Yu, Songlin; Ou, Yang; Xiao, Hongkui; Li, Jiaojiao; Adah, Dickson; Liu, Shiquan; Shu, Zhao; Li, Qin; Yao, Yongchao; Chen, Xiaoping

doi:10.1016/j.omtm.2020.03.004

Cited by 11 publications

(5 citation statements)

References 51 publications

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“…The CCR5 gene (chromosome 3 p21.31) encodes for the main HIV co-receptor. Since a bi-allelic null mutation of this receptor (CCR5Δ32) confers HIV-1 resistance and is not associated with any major pathology (Hutter et al, 2009 ), this locus was first targeted/disrupted with nucleases in T cells and HSC to provide protection against AIDS ((Perez et al, 2008 ; Yu et al, 2020 ), NCT00842634, NCT02500849, and NCT03164135) and later exploited for targeted gene addition. Therapeutic transgenes involved in lysosomal storage disorders were inserted in the CCR5 gene of human HSC, under the control of exogenous ubiquitous or tissue-specific promoters.…”

Section: Safe Genomic Harborsmentioning

confidence: 99%

Targeted Gene Delivery: Where to Land

Pavani

Amendola

2021

Front. Genome Ed.

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Genome-editing technologies have the potential to correct most genetic defects involved in blood disorders. In contrast to mutation-specific editing, targeted gene insertion can correct most of the mutations affecting the same gene with a single therapeutic strategy (gene replacement) or provide novel functions to edited cells (gene addition). Targeting a selected genomic harbor can reduce insertional mutagenesis risk, while enabling the exploitation of endogenous promoters, or selected chromatin contexts, to achieve specific transgene expression levels/patterns and the modulation of disease-modifier genes. In this review, we will discuss targeted gene insertion and the advantages and limitations of different genomic harbors currently under investigation for various gene therapy applications.

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Section: Safe Genomic Harborsmentioning

confidence: 99%

Targeted Gene Delivery: Where to Land

Pavani

Amendola

2021

Front. Genome Ed.

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“…Yu et al (9), constructed a simian immunodeficiency virus-based CRISPR-CCR5/Cas9 lentivirus to disrupt the CCR5 gene in progenitor cells collected from simian immunodeficiency virus-infected macaques and assessed the frequency of CCR5 gene editing in vivo. This study demonstrated that both single-guide RNA and dual-guide RNA-directed Cas9 could result in the disruption of CCR5 in monkey progenitor cells.…”

Section: Resultsmentioning

confidence: 99%

“…Recibido: 8 de diciembre 2022 Aceptado: 31 de enero 2023 DOI: https://doi.org/10.47307/GMC.2023.131. 1.18 ORCID: https://orcid.org/0000-0002-7243-2238 1* ORCID: https://orcid.org/0000-0001-8275-4399 2 ORCID: https://orcid.org/0000-0002-3823-4561 3 ORCID: https://orcid.org/0000-0002-5121-3335 4 ORCID: https://orcid.org/0000-0003-3745-3700 5 ORCID: https://orcid.org/0000-0003-2442-2024 6 ORCID: https://orcid.org/0000-0003-0057-2079 7 ORCID: https://orcid.org/0000-0003-4443-4938 8 ORCID: https://orcid.org/0000-0003-1104-428X 9 ORCID: https://orcid.org/0000-0002-6276-7544 10 ORCID: https://orcid.org/0000-0001-8335-4370 11 ORCID: https://orcid.org/0000-0002-6842-3064 12…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, no scoping or systematic review has summarized the evidence about the therapeutic role of CRISPR/Cas9based gene editing in HIV/AIDS therapy (8,9). Scoping studies are relevant for topics with emerging evidence like this, in which the paucity of randomized controlled trials makes it difficult for researchers to undertake systematic reviews and meta-analyses.…”

Section: Introductionmentioning

confidence: 99%

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CRISPR and gene editing in HIV therapy: A scoping review

Tuta-Quintero¹

2023

Gac Méd Caracas

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Human immunodeficiency virus (HIV) is nowadays one of the major health problems worldwide. Several strategies have been explored for the eradication of latent HIV-1 reservoirs, current antiretroviral therapy stops the progression of HIV disease, however, as new therapies are being developed, CRISPR (clustered regularly interspaced short palindromic repeats) systems have recently been used as a genome editing technique. CRISPR is becoming progressively one of the possible cures, although it remains experimental, for HIV in medical research. This systematic review summarizes literature evidence of CRISPR gene editing in HIV/AIDS therapy. This study also identifies the research gaps in the current literature, helping to guide future research.

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“…After transplantation, the CCR5-edited CD4+ T cells consistently increased in abundance and achieved basic reconstruction of the hematopoietic system. Furthermore, plasma-borne virus in one of the three monkeys became undetectable after ART cessation for seven months, and the off-target events remained undetectable (37). However, despite its safety and efficacy, another two rhesus monkeys displayed a viral rebound after ceasing ART.…”

Section: Clustered Regularly Interspaced Short Palindromic Repeats-associated Proteinmentioning

confidence: 97%

Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure

2021

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Despite the ability of combination antiretroviral therapy (cART) to increase the life expectancy of patients infected with human immunodeficiency virus (HIV), viral reservoirs persist during life-long treatment. Notably, two cases of functional cure for HIV have been reported and are known as the “Berlin Patient” and the “London Patient”. Both patients received allogeneic hematopoietic stem cell transplantation from donors with homozygous CCR5 delta32 mutation for an associated hematological malignancy. Therefore, there is growing interest in creating an HIV-resistant immune system through the use of gene-modified autologous hematopoietic stem cells with non-functional CCR5. Moreover, studies in CXCR4-targeted gene therapy for HIV have also shown great promise. Developing a cure for HIV infection remains a high priority. In this review, we discuss the increasing progress of coreceptor-based hematopoietic stem cell gene therapy, cART, milder conditioning regimens, and shock and kill strategies that have important implications for designing potential strategies aiming to achieve a functional cure for the majority of people with HIV.

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Experimental Treatment of SIV-Infected Macaques via Autograft of CCR5-Disrupted Hematopoietic Stem and Progenitor Cells

Cited by 11 publications

References 51 publications

Targeted Gene Delivery: Where to Land

Targeted Gene Delivery: Where to Land

CRISPR and gene editing in HIV therapy: A scoping review

Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure

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